Biomedical Engineering Reference
In-Depth Information
delivery (Scheme 4.10).
82
A cyclic Asn-Gly-Arg (cNGR) peptide was used to
target gene-loaded poly(lactic acid)-PEG nanoparticles into human umbilical
vein endothelial cells overexpressing CD13. The cNGR peptide could
specifically mediate the fast and efficient internalization of these nanoparticles
into the target cells.
In a study by Numata et al., silk-based block copolymers were bioengineered
both with poly(
L
-lysine) domains, to interact with plasmid DNA, and RGD, to
enhance cell-binding and transfection efficiency.
83
Samples with 30-lysine
residues and 11 RGD sequences, prepared at an N/P ratio of 2, showed the
highest transfection efficiency in HeLa cells and human embryonic kidney
cells.
Kang et al. found a PKCa-specific substrate peptide that exhibited a higher
phosphorylation ratio in tumor cells and tissues, compared with normal
tissues.
84
Moreover, they developed a novel tumor-targeted gene regulation
system responding to PKCa by using the PKCa-specific substrate peptide.
This system could distinguish between normal and tumor cells but is not tissue-
specific.
85
Recently, they developed a hepatoma-targeted gene delivery system
by combining a human liver cell-specific bionanocapsule and a tumor cell-
specific gene regulation polymer, which responds to hyperactivated protein
kinase C (PKC)a in hepatoma cells.
86
Chen et al. synthesized arginine-rich amphiphilic lipopeptides with
hydrophobic aliphatic tails (C
12
GR
8
GDS and C
18
GR
8
GDS) as functional
gene vectors (Scheme 4.11).
87
They found that these lipopeptides exhibited
very low cytotoxicity even at high concentration, and could be specifically
recognized by cancer cells due to the incorporation of RGD sequences
(specifically recognized by integrins a
v
b
3
and a
v
b
5
overexpressed on cancer
cells).
Disulfide-linked bioreducible polymers are more efficient for the intracel-
lular delivery of DNA. This increased efficiency is likely due to enhanced
decomplexation as a result of degradation of the disulfide bonds in the
reductive environment of the cytoplasm. Hyun et al. synthesized a reducible
poly(oligo-
D
-arginine) gene carrier by connecting nine-arginine oligopeptides
via internal disulfide linkages, and then mediated the heme oxygenase-1 (HO-
1) gene for the treatment of ischemia/reperfusion (I/R)-induced brain stroke.
88
This polypeptide carrier showed markedly enhanced gene transfection and
lower toxicity than 25 kDa PEI in vitro and in vivo. As the sequence of primary
d
n
4
y
3
n
g
|
3
Scheme 4.10
Synthesis of the cNGR-PEG-PLA peptide gene vector.
